Catalase-Conjugated Rose Bengal Biological Nanoparticles with Mitochondrial Selectivity Toward Photodynamic Therapy

Photodynamic therapy (PDT) has emerged as an efficient treatment for cancers in recent years. How-ever, PDT is limited by low utilization of photosensi-tizers and tumor hypoxia. The short lifetime and diffusion radius of singlet oxygen (1O2) further de -crease the anticancer effect of PDT. Herein, we design and synthesize diameter-controllable photo-sensitizer nanoparticles (NPs) which can specifically accumulate on the mitochondria of cancer cells and increase the O2 concentrations nearby to enhance PDT efficacy. Catalase (CAT) molecules are initially conjugated with rose bengal (RB) via amide bonds and then self-assembled into CAT-RB NPs. The NPs show excellent enzyme activity in catalyzing the decomposition of hydrogen peroxide into O2, which makes the yield of 1O2 1.65-fold higher than that of free RB. The intracellular uptake efficiency of NPs is increased by up to 150 times compared with pure RB. After endocytosis, the NPs mainly located at mito-chondria and 1O2 can directly destroy mitochondria under irradiation, thereby greatly decreasing the production of adenosine triphosphate and further leading to the apoptosis of cancer cells. Moreover, CAT-RB NPs can accumulate in tumors and show excellent PDT effects in vivo. This work opens a unique path to break through the current limitations of PDT in cancer treatment.